Congenital Glucagon-like Peptide-1 Deficiency in the Pathogenesis of Protracted Diarrhea in Mitchell-Riley Syndrome.

CONTEXT: Mitchell-Riley syndrome due to RFX6 gene mutations is characterized by neonatal diabetes and protracted diarrhea. The RFX6 gene encodes a transcription factor involved in enteroendocrine cell differentiation required for beta-cell maturation. In contrast to the pathway by which RFX6 mutations leads to diabetes, the mechanisms underlying protracted diarrhea are unknown. OBJECTIVE: To assess whether glucagon-like peptide-1 (GLP-1) was involved in the pathogenesis of Mitchell-Riley syndrome protracted diarrhea. METHODS: Two case report descriptions. in a tertiary pediatric hospital. "Off-label" treatment with liraglutide. We describe 2 children diagnosed with Mitchell-Riley syndrome, presenting neonatal diabetes and protracted diarrhea. Both patients had nearly undetectable GLP-1 plasma levels and absence of GLP-1 immunostaining in distal intestine and rectum. The main outcome was to evaluate whether GLP-1 analogue therapy could improve Mitchell-Riley syndrome protracted diarrhea. RESULTS: "Off-label" liraglutide treatment, licensed for type 2 diabetes treatment in children, was started as rescue therapy for protracted intractable diarrhea resulting in rapid improvement during the course of 12 months. CONCLUSION: Congenital GLP-1 deficiency was identified in patients with Mitchell-Riley syndrome. The favorable response to liraglutide further supports GLP-1 involvement in the pathogenesis of protracted diarrhea and its potential therapeutic use.

Effects of passage through the digestive tract on incretin secretion: Before and after birth.

AIMS/INTRODUCTION: It was reported that fetuses secrete endogenous incretin; however, the stimulants of fetal incretin secretion are not fully understood. To investigate the association between the passage of amniotic fluid through the intestinal tract and fetal secretion of incretin, we analyzed umbilical cord incretin levels of infants with duodenum atresia. MATERIALS AND METHODS: Infants born from July 2017 to July 2019 (infants with duodenum atresia and normal term or preterm infants) were enrolled. We measured and compared the concentrations of glucagon-like peptide-1 (GLP-1) and gastric inhibitory peptide/glucose-dependent insulinotropic polypeptide (GIP) in the umbilical vein and preprandial blood samples after birth. RESULTS: A total of 98 infants (47 term, 46 preterm and 5 with duodenum atresia) were included. In patients with duodenum atresia, umbilical vein GLP-1 and GIP levels were the same as those in normal infants. In postnatal samples, there were positive correlations between the amount of enteral feeding and preprandial serum concentrations of GLP-1 (r = 0.47) or GIP (r = 0.49). CONCLUSIONS: Our results show that enteral feeding is important for secretion of GLP-1 and GIP in postnatal infants, whereas the passage of amniotic fluid is not important for fetal secretion of GLP-1 and GIP. The effect of ingested material passing through the digestive tract on incretin secretion might change before and after birth. Other factors might stimulate secretion of GLP-1 and GIP during the fetal period.

Is adrenomedullin involved in the pathophysiology of persistent pulmonary hypertension of the newborn?

Although adrenomedullin (ADM) is a potent vasodilating peptide reported to play a possible role in the mechanisms of fetal lung differentiation and maturation, the ADM blood level in fetuses and in neonates with persistent pulmonary hypertension (PPHN) and pulmonary hypoplasia is not known. Therefore, we examined 15 patients with PPHN: 10 with congenital diaphragmatic hernia, four with congenital cystic adenomatoid malformation of the lung, and one with misalignment of pulmonary vessels with alveolar capillary dysplasia. Eight surgical patients with neonatal conditions such as intestinal atresia served as controls. Blood samples were drawn from the umbilical artery and vein at birth, and arterial blood was drawn from patients with PPHN on the 3rd and 6th days after birth. Plasma levels of ADM were measured by radiometric assay. Plasma levels of ADM in the umbilical artery and vein were elevated in patients with PPHN compared with controls, and in all groups the levels in the umbilical vein were higher than those in the umbilical artery. The arterial levels in patients with poor prognoses were elevated on the 3rd and 6th days after birth compared with those in survivors. These results indicate that ADM may be involved in the pathophysiology of PPHN and in the mechanisms of lung differentiation and/or maturation.

Fetal blood gas analysis from cordocentesis for abnormal fetal heart rate patterns.

We present three cases with abnormal fetal heart rate patterns and cordocentesis umbilical venous blood gas analyses. Conflicting heart rate patterns and cordocentesis and postnatal blood gas analyses prompt questions with regard to abnormal fetal heart rate pattern interpretation and suggest that cordocentesis blood gas analysis aids perinatal management only as a reflection of fetal status at sampling time.

Duodenal atresia: late follow-up.

In this study, 41 randomly chosen patients aged 15 to 35 years (mean 22 years) were carefully examined. As primary operations there were 13 membrane excisions, five duodenoduodenostomies, 22 duodenojejunostomies, and one gastrojejunostomy. Twenty-eight patients were symptom-free, ten admitted some discomfort, three had major pains, including one with a history of duodenal ulcer. Reoperation for adhesion ileus had been performed in six patients, in the early postoperative phase in one instance. At late follow-up barium meals (N = 41) showed completely normal findings in two cases only, hiatal hernia in two, gastritis in three, duodenogastric reflux in 12, slight dilation of the duodenum with good emptying and no reflux in 16, a huge duodenal sac in nine, diminished peristalsis in eight, delayed emptying in five, slight luminal narrowing in three, duodenal diverticuli in nine, bezoars in two, and a polyp in the duodenum of one patient. Ultrasound (N = 35) revealed a gallbladder septum in one patient and a dilated common bile duct in another; in one subject the gallbladder was not visualized satisfactorily. Isotope biligraphy (N = 15) showed biliary reflux to the stomach in 12 cases. Endoscopy (N = 20) findings were: esophagitis (1), hiatal hernia (2), gastric mucosa in the lower esophagus (2), biliary reflux (9), gastritis (7), gastric polyps (2), dilated duodenum of variable degree (19), diminished peristalsis (4), marked retention (2), abnormal papilla (3), diverticuli (4), and a persistent membrane (1). Histology showed superficial gastritis in three patients. E coli was cultured from the duodenal juice in five patients and Candida found in two.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma creatinine in neonates with atresia of the upper gastrointestinal tract.

The human fetus swallows a considerable amount of amniotic fluid which appears to be in balance with the urine output. Since amniotic fluid intake is considered to be compromised in fetuses with atresia of the upper gastrointestinal tract, glomerular function development in such infants may be delayed. Plasma creatinine level determined in 6 neonates with atresia of the upper gastrointestinal tract was similar to the level measured in neonates with lower obstruction, and both groups were within the range of values obtained during other studies in normal newborns. Glomerular functional development is probably not affected in neonates with atresia of the upper gastrointestinal tract.

[Effect of obstructive malformations on the gastrointestinal tract on bilirubin levels in newborn infants]. / Influenza delle malformazioni ostruttive del tubo gastro-intestinale sui livelli bilirubinemici del neonato.

The authors have reviewed their cases of neonatal obstructive malformations of the intestinal tract and analyzed the incidence of association with indirect hyperbilirubinemia. 39 patients in four years are considered. In 23 of them there is a bilirubin level greater than 5 mg/100 ml. A great number of high bilirubin levels (greater than 15 mg/100 ml) is associated with volvulus, malrotations and intestinal atresias. Bilirubin levels between 11 and 15 mg/100 ml are often connected with meconium ileus while ano-rectal atresias have a low bilirubin level (less than 5 mg/100 ml). The reported data allow to conclude that the jaundice is an early, but unfortunately, not specific symptom of congenital intestinal obstruction. The entero-hepatic circulation seems to be an important cause of the neonatal hyperbilirubinemia.